While the physiological characterization of primary afferent neurons has been extensive, the relevant morphological criteria that predict functional categories of these neurons have been established. The first hypothesis posed is that peptide content, in conjunction with cell diameter, peripheral target and projection of the central process in the spinal cord, can be used to classify populations of primary afferent neuron perikarya. Ultimately, this classification of neurons may be used to predict their functional properties. To examine this hypothesis, the mean diameter for each population of primary afferent perikarya that is immunoreactive for a given peptide will be determined. Co- existence of peptides in these neurons will also be characterized in order to establish the peptide signatures that discriminate the smallest populations of neurons. The nodose, trigeminal, and one lumbar ganglion believed to contain a minimum of visceral afferent neurons will be analyzed in order to determine whether specific peptide signatures are selective markers for visceral versus somatic primary afferent neurons. Whether co-existence of peptides in primary afferent neurons is a plastic phenomenon, and therefore a reliable criterion, will be examined by comparing the frequency of co-existence in ganglia from normal animals to ganglia from an animal model for chronic pain. Preliminary correlations of peptide signatures with primary afferent neurons associated with A-delta or C fibers will be based on the diameter of the neuron, the pattern of distribution of peptide immunoreactive axons of primary afferent origin in the spinal cord, and whether the axons are capsaicin sensitive. The second hypothesis to be tested is that axons of primary afferent neurons may contain presynaptic receptors for some of the peptides that occur in the highest frequency in these neurons. In vitro receptor autoradiography will be used to determine a correlation of selected peptide binding sites with primary afferent fibers. To determine whether these binding sites reflect functional receptors, changes in the density of peptide binding sites will be determined in the spinal cord as a function of chronic pain, a physiological stimulus for the small diameter primary afferent fibers known to contain the peptides. Data from these studies will provide a meaningful classification of primary afferent perikarya and provide insights into the functional significance of some peptides contained within these neurons, particularly with respect to nociceptive systems.